L312/Spring 2007Lecture 4Drummond

1
L312/Spring 2007 Lecture 4 Drummond

• Housekeeping issues In-class analogy exercise
  today (5 poins)
• Dont forget about next Tuesdays drawing
  assignment.
• I will post the first half of a study guide
  this week (1-4)
• Review key points
• a. Phospholipids spontaneously form a small
  spherical bilayer in aqueous solution
• impermeable to proteins, ions, most small
  molecules (hydrophobics pass) even water
• b. Lipid bilayer itself is highly flexible
  anchored by protein networks (cytoskeleton)
• c. 25 nm liposome bilayer is much smaller,
  different shape compared with cells
• d. Phospholipids and cholesterol have an
  amphipathic molecule structure
• e. Membranes are asymmetric fed from inside
  bilayer into inner sheath
• flippases maintain distribution (ATP dependent)
• vesicular transport same membrane face always
  faces cytoplasm
• supports extracellularization of carbohydrate
  face, among other features

Today consider transmembrane structures and
membrane roles. FRAP (fluorescence recovery
after photobleaching) can be used
to characterize difffusion of fluorescently
labeled molecules in membrane describe movement
of materials across membranes Movement of glucose
across membranes
2
What are the essential roles of membranes within
cells?
(no physical transport)
Flexibility (are all membranes basically the
same?)
(highly selective physical transport)
Show NEW FRAP movie Think about movement within
the membrane
3
Next wave transporting molecules across cell
membranes

• Focus on three general strategies (others exist)
• Passive diffusion transporter is simply a
  channel that allows
• flow of a single component down a concentration
  gradient (favorable)
• may still be gated (open/closed). Example K
  channel or H20 channel).
• Symport still passive diffusion down a
  concentration gradient, but
• the process is coupled with an unfavorable
  transport. Example
• the glucose/Na system for glucose uptake.
• 3. Active transport. An energy source such as
  ATP is used to drive uptake
• (or export) of a molecule against a
  concentration gradient.
• (Movement is unfavorable without ATP hydrolysis,
  which is favorable).
• What kinds of transmembrane structures support
  selective transport?

4
What are the general classes of membrane
associated proteins?
5
Review of membrane-spanning helical structure
(what are the essential side chain
properties?)
6
Multiple membrane-spanning helices can form a
pore/transporter
Carefully note inside/outside relationships here.
7
What kinds of molecules, and over which membranes?
8
A passive diffusion pore (can be gated to open
and close)
Examples K, water, Ammonia, glycerol,
others Why not bigger molecules?
What are the key mechanistic Features? Which way
does K flow? Why?
9
Glucose uptake as a model system to study small
molecule transport
Why the shape Of the villi? Note cellular
Structure here.
Pay REALLY close attention to the three
transporters and the driving force for each
directional movement
10
The three classes of transporters used here
Glucose deposition In the extracellular fluid
Na/K exchange On the inside
Glucose uptake from the intestinal lumen
11
Another example of a passive movement across a
membrane
What are the two key features Conferred by the
transporter?
12
Scooby Doo and the Mummy (or the magic fridge
commercial)
Scooby and Shaggy are wandering around in a room
with a bookcase Together they lean up against
the bookcase Suddenly the bookcase whirls
around Scooby and Shaggy disappear from
room Scooby and Shaggy are presumed to be
deposited in the adjacent room
13
Coupled transport a sodium gradient is used to
concentrate glucose
What are the key elements of successful
transport? Are transporters enzymes? What is an
enzyme? What makes this process sustainable?
14
Glucose uptake as a model system to study small
molecule transport
Why the shape Of the villi? Note cellular
Structure here.
Pay REALLY close attention to the three
transporters and the driving force for each
directional movement
15
What happens to glucose that builds up in the
cell?
What maintains a low Glucose concentration in the
Extracellular fluid here?
Uniport!
16
What drives sodium back outside the cell?
(subtext against a gradient)
Why is ATP essential? What does it really
do? Why is the advantage to being an
exchanger (Na for K exchange) What happens to
the K (Figs 12.19,20)?
Antiport! (mousetrap?)
17
FRAP how can we measure lateral diffusion
in a membrane?
18
What structures might restrict lateral diffusion
in a membrane?
How does this relate to cellular or organellar
structure? How might restriction of protein or
lipid movement support cell physiology?
19
The extracellular surface is coated with
carbohydrates
Note that carbohydrates are linked to both lipids
and proteins. How did they get outside the cell?
20
What is one role for the surface carbohydrates on
cells?
How flexible are membranes? How squishable are
cells? (how small a diameter hole could a cell
fit through?)
In-class How might cells pass between layers
of cells in a tissue? What are the key structural
properties of cells that allow this to occur?
21
If flip-flop is slow (how slow?), how rapid is
lateral diffusion?
Ask about lipids AND proteins
22
How can the energy released from ATP hydrolysis
be used to drive transport?